The overall aim of the NSABP cooperating institutions has been, and continues to be, improvement in the duration and quality of survival of patients with primary operable carcinoma of the breast. To date we have demonstrated the effectiveness of single (L-PAM) and multiple (L-PAM + 5-FU and L-PAM + 5-FU + tamoxifen) chemotherapeutic agents in decreasing recurrence rates and increasing survival in patients with primary breast cancer and axillary nodal metastases, following adequate surgical therapy. This has been done through prospective, randomized, controlled clinical trials, (B-05, B-07, B-08, B-09). We will continue to follow these patients and analyze the data with regard to efficacy and long term toxicity of adjuvant chemotherapy. The prospective, randomized, controlled clinical trial will also be used to test two other specific hypotheses with regard to the adjuvant treatment of primary operable breast cancer. First, the addition of adriamycin to PF or PFT further decreases recurrence rates and improves survival rates in these patients, (Protocols B-11 and B-12). Second, post-operative adjuvant chemotherapy can decrease recurrence and increase survival following mastectomy in patients with primary operable breast cancer without axillary nodal metastases, (B-13 and B-14). Protocol B-13 will test sequential methotrexate -- 5-FU (in patients whose tumors do not contain estrogen receptor protein) versus no post-operative therapy. Protocol B-14 will test the efficacy of the anti-estrogen tamoxifen against a post-operative placebo in patients whose tumors do contain estrogen receptor protein. Also, the clinical trial is being used to assess the biologic significance of multicentricity in breast cancer by comparing segmental mastectomy to modified radical mastectomy in suitable patients with primary operable breast cancer, (Protocol B-06).